title: Involvement of renal sympathetic nerve overactivation in the progression of chronic kidney disease in rats.
abstract: Time-dependent changes in the renal sympathetic nerve activity (RSNA) in the progression of chronic kidney disease (CKD) have not been investigated, despite the fact that renal sympathetic nervous system is augmented in the condition of CKD. In the present study, we examined time-dependent changes in RSNA and renal venous norepinephrine concentrations for 12 weeks using 5 of 6 nephrectomized CKD rats. Both RSNA and norepinephrine concentrations were increased during the early phase in the progression of CKD. Urinary protein excretion and systolic blood pressure (SBP) were gradually increased during 12 weeks after 5 of 6 nephrectomy. Treatment with γ-aminobutyric acid or the combination of prazosin and propranolol in the early phase (0-4 weeks) after 5 of 6 nephrectomy significantly attenuated the increases in urinary protein excretion and SBP in 5 of 6 nephrectomized rats. On the other hand, the same treatment in the late phase (8-12 weeks) after 5 of 6 nephrectomy failed to suppress the proteinuria and increase in SBP. Treatment with hydralazine at hypotensive dose for 12 weeks also failed to affect the proteinuria in 5 of 6 nephrectomized CKD rats. In conclusion, the augmentation of renal sympathetic nervous system in early phase after 5 of 6 nephrectomy is closely related to the development of partial ablation-induced CKD in rats.
authors.affiliation: *Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe, Hyogo, Japan; †Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan; ‡Laboratory of Clinical Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Osaka, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Kobuchi
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Tanaka
authors.forename: Asami
authors.initials: A
authors.lastname: Funai
authors.forename: Rie
authors.initials: R
authors.lastname: Suzuki
authors.forename: Maki
authors.initials: M
authors.lastname: Yazawa
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ohkita
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Ayajiki
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Matsumura
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001342:Autonomic Nervous System Diseases / Q000503:physiopathology*; D001794:Blood Pressure / Q000502:physiology; D018450:Disease Progression; D018682:GABA Agents / Q000494:pharmacology; D006830:Hydralazine / Q000494:pharmacology; D007668:Kidney / Q000294:innervation; D007677:Kidney Function Tests; D008297:Male; D009392:Nephrectomy; D009638:Norepinephrine / Q000378:metabolism; D010525:Peripheral Nerves / Q000502:physiology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D018682:GABA Agents; D006830:Hydralazine; D005680:gamma-Aminobutyric Acid; D011433:Propranolol; D009638:Norepinephrine; D011224:Prazosin